Table 1.
Preclinical studies and early clinical trials for PXE (and GACI).
| Treatment/Therapy | Rationale/Target | Diagnosis | References |
|---|---|---|---|
| Correction, replacement, or inhibition of dysfunctional genes/proteins | |||
| PTC-124 (Ataluren or Translarna) | Allows read-through of PTC codons, targets nonsense mutations | PXE | [131] |
| 4-Phenylbutyrate (4-PBA) | Corrects missense mutations allowing for correct cellular localization | PXE | [80,99,117] |
| Rh-NPP1-Fc | Replacement for ENPP1 | GACI | [89,132,133] |
| SBI-425 (TNAP inhibitor) | Inhibits the enzymatic activity of TNAP | PXE | [20,127] |
| Fetuin-A | Glycoprotein that forms complexes with calcium and phosphate ions, acts as an inhibitor of ectopic calcification | PXE | [134,135] |
| Adenovirus with ABCC6 cDNA | Transiently express ABCC6 in the liver | PXE | [136] |
| Bevacizumab (Anti-VEGF) † | Anti-angiogenic therapy; Preserves ocular function in advanced and early disease stages | PXE | [24] |
| Supplementation therapies for direct inhibition of calcification | |||
| Sevelamer hydrochloride (Renagel) | Phosphate binder | PXE | [130,137] |
| Magnesium | Inhibits the formation of apatite | PXE | [129,138,139] |
| Vitamin K (phylloquinone/menaquinone) | Correct for insufficient carboxylation of matrix gla protein (MGP) | PXE | [92,115,116,140,141,142,143] |
| Bisphosphonate (etidronate *, zoledronate) | Non-hydrolyzable analog of PPi, inhibits enzymes that utilize pyrophosphate | PXE and GACI | [18,55,126,144,145,146,147,148] |
| Pyrophosphate * | Potent inhibitor of calcification, ABCC6 modulates PPi production | PXE | [18,19,120], PROPHECI |
| INS-3001 (IP6 derivative) | Known inhibitor of calcification | PXE | [149] |
| Sodium thiosulfate | Approved for calciphlaxis | PXE | [59] |
* Denotes treatments undergoing clinical trials, † currently in use in PXE patients. PXE, pseudoxanthoma elasticum; GACI, generalized arterial calcification of infancy; MGP, matrix gla protein; PPi, pyrophosphate.